دورية أكاديمية
أعرض في EDS

Phase 1a dose escalation study of ivonescimab (AK112/SMT112), an anti-PD-1/VEGF-A bispecific antibody, in patients with advanced solid tumors.

التفاصيل البيبلوغرافية
العنوان: Phase 1a dose escalation study of ivonescimab (AK112/SMT112), an anti-PD-1/VEGF-A bispecific antibody, in patients with advanced solid tumors.
المؤلفون: Frentzas S; Department of Medical Oncology, Monash Health, Melbourne, Victoria, Australia.; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia., Austria Mislang AR; Icon (Adelaide) Cancer Centre, Kurralta Park, South Australia, Australia.; Flinders Centre for Innovation in Cancer, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia., Lemech C; Scientia Clinical Research Ltd, Sydney, New South Wales, Australia., Nagrial A; Blacktown Cancer and Haematology Centre, Blacktown Hospital, University of Sydney, Sydney, New South Wales, Australia., Underhill C; Border Medical Oncology and Haematology Research Unit, Albury-Wodonga Regional Cancer Centre, Albury Wodonga, New South Wales, Australia.; University of New South Wales, Rural Medical School, Albury Campus, Sydney, New South Wales, Australia., Wang W; Akeso Biopharma, Inc, Zhongshan, China., Wang ZM; Akeso Biopharma, Inc, Zhongshan, China., Li B; Akeso Biopharma, Inc, Zhongshan, China., Xia Y; Akeso Biopharma, Inc, Zhongshan, China., Coward JIG; Icon Cancer Centre, Brisbane, Queensland, Australia jim.coward@icon.team.; Faculty of Medicine, University of Queensland, St Lucia, Queensland, Australia.
المصدر: Journal for immunotherapy of cancer [J Immunother Cancer] 2024 Apr 19; Vol. 12 (4). Date of Electronic Publication: 2024 Apr 19.
نوع المنشور: Clinical Trial, Phase I; Journal Article
اللغة: English
بيانات الدورية: Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101620585 Publication Model: Electronic Cited Medium: Internet ISSN: 2051-1426 (Electronic) Linking ISSN: 20511426 NLM ISO Abbreviation: J Immunother Cancer Subsets: MEDLINE
أسماء مطبوعة: Publication: 2020- : London, United Kingdom : BMJ Publishing Group Ltd.
Original Publication: London : BioMed Central, 2013-
مواضيع طبية MeSH: Antibodies, Bispecific*/adverse effects , Neoplasms*/drug therapy, Humans ; Antibodies, Monoclonal, Humanized/adverse effects ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Hypertension/chemically induced ; Immune Checkpoint Inhibitors/therapeutic use ; Lung Neoplasms/drug therapy ; Programmed Cell Death 1 Receptor/therapeutic use ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A
مستخلص: Background: Studies showed that vascular endothelial growth factor (VEGF) inhibitors could improve therapeutic efficacy of PD-1/PD-L1 antibodies by transforming the immunosuppressive tumor microenvironment (TME) into an immunoresponsive TME. Ivonescimab is a first-in-class, humanized tetravalent bispecific antibody targeting PD-1 and VEGF-A simultaneously. Here, we report the first-in-human, phase 1a study of ivonescimab in patients with advanced solid tumors.
Methods: Patients with advanced solid tumors were treated with ivonescimab 0.3, 1, 3, 10, 20 or 30 mg/kg intravenously every 2 weeks using a 3+3+3 dose escalation design. Dose expansion occurred at 10 and 20 mg/kg in selected tumor types. The primary objective was to assess the safety and tolerability, and to determine the maximum tolerated dose (MTD). The secondary objectives included pharmacokinetics, pharmacodynamics and preliminary antitumor activity based on Response Evaluation Criteria in Solid Tumors V.1.1.
Results: Between October 2, 2019 and January 14, 2021, a total of 51 patients were enrolled and received ivonescimab. Two dose-limiting toxicities were reported at 30 mg/kg. The MTD of ivonescimab was 20 mg/kg every 2 weeks. Grade≥3 treatment-related adverse events (TRAEs) occurred in 14 patients (27.5%). The most common TRAEs of any grade were rash (29.4%), arthralgia (19.6%), hypertension (19.6%), fatigue (17.6%), diarrhea (15.7%) and pruritus (11.8%). The most common grade≥3 TRAEs were hypertension (7/51, 13.7%), alanine aminotransferase increased (3/51, 5.2%), aspartate aminotransferase increased (2/51, 3.9%) and colitis (2/51, 3.9%). Of 47 patients who had at least one postbaseline assessment, the confirmed objective response rate was 25.5% (12/47) and disease control rate was 63.8% (30/47). Among 19 patients with platinum-resistant ovarian cancer, 5 patients (26.3%) achieved partial response (PR). Efficacy signals were also observed in patients with mismatch repair proficient (pMMR) colorectal cancer, non-small cell lung cancer, and both MMR deficient and pMMR endometrial cancer.
Conclusions: Ivonescimab demonstrated manageable safety profiles and promising efficacy signals in multiple solid tumors. Exploration of alternative dosing regimens of ivonescimab monotherapy and combination therapies is warranted.
Trial Registration Number: NCT04047290.
Competing Interests: Competing interests: WW, ZMW, BL, and YX are all employees of Akeso Biopharma, Zhongshan, China. JIGC provided consultancy work for Akeso since 2022. The other authors declare no potential conflicts of interest.
(© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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فهرسة مساهمة: Keywords: antibodies, neoplasm; clinical trials as topic
سلسلة جزيئية: ClinicalTrials.gov NCT04047290
المشرفين على المادة: 0 (Antibodies, Bispecific)
0 (Antibodies, Monoclonal, Humanized)
0 (Immune Checkpoint Inhibitors)
0 (Programmed Cell Death 1 Receptor)
0 (Vascular Endothelial Growth Factor A)
تواريخ الأحداث: Date Created: 20240420 Date Completed: 20240422 Latest Revision: 20240522
رمز التحديث: 20240523
مُعرف محوري في PubMed: PMC11033648
DOI: 10.1136/jitc-2023-008037
PMID: 38642937
قاعدة البيانات: MEDLINE
الوصف
تدمد:2051-1426
DOI:10.1136/jitc-2023-008037